Tumor chemoprevention and treatment are two approaches aimed at improving the survival of patients with cancers. An ideal anti-tumor drug is that which not only kills tumor cells but also alleviates tumor-causing risk factors, such as precancerous lesions, and prevents tumor recurrence. Chinese herbal monomers are considered to be ideal treatment agents due to their multi-target effects. Astragaloside has been shown to possess tumor chemoprevention, direct anti-tumor, and chemotherapeutic drug sensitization effects. In this paper, we review the effects of astragaloside on tumor prevention and treatment and provide directions for further research.
Humans ; Chemoprevention ; Antineoplastic Agents ; Neoplasms/prevention & control* ; Saponins/pharmacology* ; Triterpenes/pharmacology*

Objective:To evaluate the potential of a previously identified CDR3 only single-domain antibodies (sdAbs) fragment, NBL42, as a general framework for affinity transfer.Methods:The H3 loops of VHH-A4(A4), VHH-H5(H5), cAb-Lys3(L3) and B6H12 which bind with alliinase, PD-1, lysozyme and CD47, respectively, were grafted into the corresponding loop of NBL42. The genes of the reconstituted CDR3 only sdAbs were synthesized, expressed in E. coliand purified with Ni 2+ column affinity chromatography. The antigen binding and stability of the recombinant CDR3 only sdAbs were assayed by ELISA. Results:The recombinant NBL42-A4CDR3, NBL42-H5CDR3, NBL42-L3CDR3 and NBL42-B6H12CDR3 ran as a single peak at 15, 15, 28 and 16 kDa, respectively, in SDS-PAGE as expected molecular weight. Grafted sdAbs NBL42-A4CDR3 and NBL42-H5CDR3 expressed in a soluble form and specifically bind with alliinase and PD-1, respectively, but lost about 50% of their binding activity. In contrast, the grafted sdAbs NBL42-Lys3CDR3 and NBL42-B6H12CDR3 completely lost their antigen binding capacity. NBL42 sdAbs and grafted sdAbs NBL42-A4CDR3 and NBL42-H5CDR3 retain roughly half of their binding activity after 90 ℃ heat treatment, indicating high stability. The C88Y mutation in NBL42 and the Swiss Mode 3D model predicted that the C88Y residue in FR3 may play a key role in NBL42 stability and CDR3 affinity transfer.Conclusions:The structure of NBL42 has potential as a framework for CDR3 transplantation and affinity transfer.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Objective The study was to investigate the activation of tumor necrosis factor α (TNF-α) mRNA transcription and protein expression in peripheral blood and activation of signal path PI3K/AKT in patients with chronic heart failure. Methods From February 2015 to April 2018, 244 patients with heart failure in the cardiovascular department of our hospital were selected as heart failure group, while 244 healthy cases were enrolled as the control group at the same time. The peripheral blood samples of two groups were collected. We detected the transcription and protein expression of TNF-α mRNA and the activation of PI3K, AKT in peripheral blood. The left ventricular ejection fraction (LVEF) were measured in two groups. The correlations between influencing factors and LVEF were analyzed. Results The levels of PI3K, AKT in the heart failure group were higher than those in the control group. The differences were statistically significant respectively (P < 0.05). The mRNA relative content and protein content of TNF-α in peripheral blood mononuclear cells of heart failure group were higher compared with those of control group (P < 0.05). The LVEF of heart failure group was significantly lower than that of the control group (34.50 ± 6.33) ％ versus (55.60 ± 2.49) ％, P < 0.001). Among 244 patients with heart failure, Spearman correlation analysis showed that there were significant positive correlations between TNF-a mRNA and protein expression levels and the levels of PI3K, AKT respectively (P < 0.05). Multiple factors unconditional Logistic regression analysis showed that the TNF-α mRNA, protein expression and PI3K, AKT levels in peripheral blood were independent risk factors for LVEF (P < 0.05). Conclusion The expression levels of PI3K, AKT and TNF-α are all significantly increased in chronic heart failure patients, which could participate in the occurrence and development of heart failure.

Objective: To investigate the different surgical approaches and long-term outcomes of endoscopy-assisted transoral removal of deep hilar and intraparenchymal stones in the Wharton′s duct. Methods: From January 2008 to March 2018, 481 consecutive patients with deep hilar and intraparenchymal calculi in the Wharton′s duct underwent endoscopy-assisted transoral removal at Deparment of Oral and Maxillofacial Radiology, Peking University School and Hospital of Stomatology. There were 250 males and 231 females. Their ages ranged from 9-86 years. We operated 476 patients under local anesthesia on an outpatient basis, and the remaining 5 were operated under general anesthesia. On the basis of ultrasonography, spiral CT, sialography and endoscopy, the calculi were classified into 4 types: hilum stones (located at the hilum or proximally with a distance <5 mm from the hilum), infra-hilum stones (intra-glandular stones with a distance of 5-10 mm from the hilum), intraparenchymal stones (with a distance ≥10 mm from the hilum), and multiple stones (concomitant hilum and intra-glandular stones). The treatment approaches included: hilum duct slitting, intraparenchymal duct slitting, submandibulotomy and intraductal retrieval. The success rate, immediate safety and effectiveness of different types of stones were evaluated. After surgery, the patients were followed up, and gland function was analyzed on the basis of clinical symptoms and signs. Results: The calculi sizes varied from 3 to 25 mm, with a mean of 7.8 mm. The calculi were located in the right submandibular gland in 259 patients, in the left submandibular gland in 219 patients and in bilateral glands in 3 patients. The calculi were successfully removed in 446 glands, with a success rate of 92.1% (446/484). The success rate varied according to the stone sites: 97.8% (363/371) for hilum stones, 64.4% (29/45) for infra-hilum stones, 4/16 for intraparenchymal stones and 96.2% (50/52) for multiple stones. The main treatment methods applied included hilum duct slitting in 347 glands, intraparenchymal duct slitting in 13, submandibulotomy in 4, intraductal retrieval in 73, and hilum duct slitting accompanied by intraductal retrieval in 9. Ductal breakage occurred in 2 glands. All patients complained of mild to moderate pain with a duration of 3-7 days. Nine had temporal lingual nerve injury. During 3-120 months′ follow-up (mean 36 months) of the total 484 glands, 1.6% (7/446) developed ranula, 1.3% (6/446) experienced obturation of the main duct and 2.0% (9/446) had recurrent stones. The remaining 95.1% (424/446) glands were symptom-free with good function. Conclusions Endoscopy-assisted transoral removal of deep hilar and intraparenchymal submandibular calculi is a safe and effective gland-preserving procedure. According to the depth, size and number of the calculi, variant surgical approaches should be attempted to maximize the success rate and to minimize the side effects.

OBJECTIVE:To investigate the protective effect of the compatibilities of ginsenosides Rg1 and aconitine on myocar-dial cell of in vitro cultured heart failure model. METHODS:The myocardial cells of neonate rat were grouped into normal control group,model group,positive control group(Deslanoside injection,1×10-7 mol/L),ginsenosides Rg1 group(1×10-8 mol/L),acon-itine group (1 × 10-9 mol/L) or their compatibilities groups (1∶1,2∶1,1∶2,V/V). Except for normal control group,other groups were given 0.8%pentobarbital sodium to induce heart failure model of myocardial cells. After modeling,each group was given rele-vant medicine for 1 h,and then the activities of T-ATPase,Ca2+-Mg2+-ATPase,Na+-K+-ATPase in cells were all detected. The activi-ties of acyl carrier protein(ACP)and lactate dehydrogenase(LDH),and the contents of brain natriuretic party(BNP),TNF-α and total glycogen were measured in cell culture fluid. RESULTS:Compared with normal control group, T-ATPase and Ca2+-Mg2+-ATPase activities were decreased significantly in model group;meanwhile,Na+-K+-ATPase activity was increased signifi-cantly,and ACP,LDH activities and BNP content in cell culture fluid were increased significantly(P<0.05). Compared with mod-el group,the activities of T-ATPase in treatment groups were increased significantly,while the activity of LDH in cell culture fluid was decreased significantly;when the volume ratio of ginsenoside Rg1 to aconitine was 2∶1,protective effect was the strongest;the activities of Na+-K+-ATPase in aconitine group and compatibility groups were all decreased significantly,with statistical signifi-cance(P<0.05). The activities of ACP and BNP in cell culture fluid were all decreased in treatment groups,but the content of to-tal glycogen in cells and the TNF-α content of in cell culture fluid had no change (P>0.05). CONCLUSIONS:Compatibility of ginsenosides Rg1 and aconitine can improve ATPase activities and membranous permeability,regulate BNP secretion and protect myocardial cell of heart failure model,especially the compatibility of ginsenosides Rg1 to aconitine of 2∶1 ratio.

Objective To discuss the application form, method and effect of blending learning based on MOOC in Obstetrics and Gynecology Nursing Course, so as to improve learning quality and com-prehensive qualities of students. Methods Randomly selected a nursing undergraduate class as experi-mental group (n=190) and another as control group (n=189);blending learning and traditional teaching model were adopted, respectively. T test and chi-square test were used to compare scores of final exam in two groups, and Rating Scale of Self-directed Learning Competence for Nurses and Scale of Clinical Commu-nication Competence for Nursing Students were used to evaluate two groups before and after the course. Results The average score (76.30±7.08) and excellent rate (35.79％) in the experimental group were higher than those in the control group of (74.78 ±7.18) and 25.93％, with significance differences (P<0.05);Surveys showed that after the course, the autonomous learning ability and the clinical communication ability of students in the experimental group were better than before, and were better than those in the control group. Conclusion Blending learning can be applied to Obstetrics and Gynecology Nursing Course, which can effectively improve learning quality and enhance students' ability of independent study and clinical com-munication, with satisfactory teaching effects to both teachers and students.

Objective To investigate antimicrobial resistance among nosocomial gram-negative bacilli in 2006.Methods About 987 consecutive and non-repetitive gram-negative bacilli were isolated from 10 teaching hospitals from Sep.to Dec.in 2006 in China.All of these isolates were sent to the central laboratory for reidentification and susceptibility testing.The minimal inhibitory concentration(MICs)of meropenem and other antibacterial agents were determined by agar dilution method.Results The activity of antibacterial agents against Enterobacteriaceae was as fol lows in descending order of susceptible rate: meropenem(susceptible rate 99.8%),imipenem(99.5%),piperacillin/tazobactam(91.3%),amikacin (89.3%),cefepime(83.8%),cefoperazone/sulbactam(79.7%),ceftazidime(74.7%),cefotaxime (57.7%),ceftriaxone(56.6%),ciprofloxacin(53.6%).The prevalence of extended-spectrum β-Iactamases(ESBL)was 59.0% in Escherichia coli,33.0%in Klebsiella pneumoniae and 8.0%in Proteus mirabilis.The most active agents against E.coli and K.pneumoniae were meropenem,imipenem(99.2%. 100%),piperacillin/tazobactam(90.8%-97.0%),and amikacin(83.8%-92.4%).Cefepime Was more active against K.pneumoniae than E.coli(85.4% vs.65.2%).Against E.cloacae,E.aerogenes and Citrobacter freundii,the most active agents were as follows in desecnding order:meropenem,imipenem (99.2%-100%),amikacin(85.2%-92.6%),cefepime(81.5%-85.9%),piperacillin/tazobactam (73.4%-87.2%),cefoperazone/sutbactam(65.6%-77.7%),and ciprofloxacin(53.1%-72.3%).The most active agents against Pseudomonas aeruginosa were amikacin(83.5%),followed by meropenem (79.1%),piperacillin/tazobactam(74.1%),and imipenem(70.9%).The most susceptible agents against Acinetobacter baumannii were imipenem(79.1%),meropenem(73.4%) and cefoperazone/ sulbaetam(54.7%).Mutiresistant A.baumannii increased up to 53.0%.The most active agents against Burkholderia cepacia were meropenem(73.3%),eeflazidime(73.3%),and piperacillin/tazobactam (62.2%).Conclusions Carbapenems remained very high activity against Enterobacteriaceae.Increasing resistance to 10 antimicrobials agents tested from A.baumanni and P.aeruginosa brought great concern.

OBJECTIVE To investigate the antimicrobial resistance of hospital-and community-acquired pathogens collected from 10 teaching hospitals located at different areas in China in 2006.METHODS According to the study protocol,the strains of Streptococcus pneumoniae,meticillin-susceptible Staphylococcus aureus(MSSA),Escherichia coli and Klebsiella pneumoniae were collected and sent to the central lab for reidentification and susceptibility testing.The minimal inhibitory concentrations(MICs) of antimicrobial agents against Str.pneumoniae were determined by Etest method and MICs of antimicrobial agents against S.aureus,E.coli and K.pneumoniae strains were determined by agar dilution method.WHONET5.4 software was used to analyze the data.RESULTS Among 353 Str.pneumoniae strains,74.2% were penicillin-susceptible(PSSP),9.6% were penicillin-intermediate(PISP) and 16.2% were penicillin-resistant(PRSP).Strains from different hospitals showed different sensitivity to penicillin.Among ?-lactam antibiotics,cefuroxime showed the lowest susceptibility rate of 0%(for PRSP) to 76.7%(for PSSP).The susceptibility rate to ceftriaxone and amoxicillin-clavulanic acid was 98.1% and 98.9% in PSSP group,61.8% and 64.7% in PISP group,and 15.8% and 10.5% in PRSP group.The ESBLs rate was 56.2% among 267 Escherichia strains and 42.7% among 206 K.pneumoniae strains.For ESBLs-producing strains,the susceptibility rates to cefotaxime and ceftriaxone were low and the rate to ceftazidime was relatively high among ?-lactam antibiotics.73.4% MSSA strains produced ?-lactamase.?-Lactam antibiotics tested showed high susceptibility against MSSA strains.The susceptibility rate was 98.9-100%.The susceptibility rate to ciprofloxacin and levofloxacin was 80.8% and 88.1%,separately.CONCLUSIONS Fluoroquinolones show high susceptibility against Str.pneumoniae.Ceftriaxone and amoxicillin-clavulanic acid have relatively high susceptibility among ?-lactams.For MSSA and non-ESBLs-producing E.coli and K.pneumoniae strains,?-lactams show high susceptibility.For ESBLs-producing E.coli and K.pneumoniae strains,the susceptibility rates to cefotaxime and ceftriaxone are low and that to ceftazidime,cefepime and cefoperazone-sulbactam are relatively high.

80% activity rate against E.coli included piperacillin/tazobactam(93.4%)、ceftazidime(86%),and amikacin(83.3%);The susceptible rate to piperacillin/tazobactam in K.pneumoniae was 84.6%. The susceptible rate to ceftazidime decreased from 82.3% to 69.9%, which was lower than to cefepime (77.2%). Over 50% of Enterobacter cloacae were resistant to ceftazidime, cefotaxime and ceftriaxone. Susceptible rates to piperacillin/tazobactam in E. cloacae,E. aerogenes,Citrobacter freundii and Serratia marcescens (67.7%-96.4%) were higher than those to cefepime (68.8%-77.5%), cefoperazone/sulbactam (59.7%-87.5%). Susceptibility to amikacin among these 4 species (70%-83.7%) was higher than to ciprofloxacin (48.1%-79.5%). All of Morganella morganii and Proteus vulgaris isolates were susceptible to meropenem and imipenem; Over 90% of the isolates were susceptible to cefepime, cefoperazone/sulbactam and piperacillin/tazobactam.The most active agent against Pseudomonas aeruginosa was meropenem (84%), followed by amikacin, piperacillin/tazobactam, ceftazidime and imipenem (72.5%-76.6%). Mutiple-drug-resistant Acinetobacter baumannii increased from 33% in 2003 to 48% in 2004. Resistance to carbapenems increased to 18% in this species in 2004. The most active agents against Burkholderia cepacia were meropenme (64.9%), cefoperazon/sulbactam (63.2%), ceftazidime (59.6%), piperacillin/tazobactam (56.1%) and cefepime (52.6%).Conclusions Carbapenems remained very high activity against Enterobacteriaceae. Increasing resistance to 10 antimicrobials agents tested among A. baumanni brought great concern. Meropenem was 4-to 16-fold more active against common gram-negative bacilli than imipenem.